Current clinical techniques used to determine glomerular filtration rate (GFR) are based on the concept of clearance. Under normal steady-state conditions, the daily production of creatinine is equal to the daily excretion of creatinine, regulating serum creatinine within a narrow range. Thus, clinicians frequently use serum creatinine concentration alone as an estimate of the GFR. However, this technique has limited accuracy and the presence of unllateral kidney disease is usually not detectable. Even moderate degrees of renal insufficiency can be masked by a serum creatinine concentration falling within the normal range. Thus, a reduction in GFR of up to 50% may occur in conjunction with a normal serum creatinine concentration.
Direct measurement of clearance frequently provides a better indicator of renal status than serum creatinine, particularly in early stages of renal disease. If the clinical suspicion of renal dysfunction is high, a more exact determination of GFR by endogenous creatinine clearance will provide a more accurate assessment of renal function. The use of these conventional clearance methods requires the collection of multiple urine and blood samples and, in theory, requires steady-state conditions to approximate GFR. Renal clearances can also be measured during maintenance of a constant concentration of inulin in the plasma. Inulin has been established as the ideal reference material because as the volume of distribution of the marker remains constant with constant infusion, it is freely filtered and is neither reabsorbed nor secreted. Other exoganous substances have been used as markers for the evaluation of renal clearance and include chelating compounds such as DTPA (diethylene triamine pentaacetic acid), exogenous creatinine, sodium lothalamate and vitamin B12.
The disadvantages of conventional clearance techniques are that they require timed urine collections which do not accurately reflect changing urine flow rates, acute changes in renal functions, variations in residual bladder volume, changes in reabsorption of the marker at markedly reduced urine flows, variations in protein binding of the marker and plasma, presence of drugs that compete with the marker for excretion, degradation or synthesis of the marker in the kidney and variation of clearance rates with a marker concentration that exceeds a reabsorptive or secretory transport maximum. Conventional clearance techniques requiring urine collections are not feasible in conditions of partial or total cessation of urine flow. This can occur in dehydrated states or during obstructive uropathy.
Some of the limitations of conventional clearance techniques can be overcome with a more invasive method using the plasma extraction ratio (filtration fraction) of inulin, creatinine or DTPA compounds multiplied by the plasma flow. The arteriovenous determination of glomerular filtration rate (GFR) is the product of the filtration fraction (FF) and renal plasma flow (RPF): EQU GFR=FF.times.RPF (1)
Filtration fraction can be expressed as: ##EQU1## where Ca is the contrast medium concentration in the renal artery and Cv is the contrast concentration in the renal vein. This measure of renal function encompasses both the extraction efficiency of the kidney and the amount of blood being filtered. It is a simple and rapid determination of single kidney function that is independent of timed urine collections.
Magnetic resonance measurement of blood flow has been demonstrated using a phase sensitive method. Magnetic resonance has also been demonstrated as a method to measure renal clearance using relaxation measurements in in-vitro serum and urine samples.